NO329351B1 - Substituerte tiofener, anvendelse derav samt legemiddel for human- eller veterinaermedisinsk anvendelse - Google Patents

Info

Publication number

NO329351B1

NO329351B1 NO20045504A NO20045504A NO329351B1 NO 329351 B1 NO329351 B1 NO 329351B1 NO 20045504 A NO20045504 A NO 20045504A NO 20045504 A NO20045504 A NO 20045504A NO 329351 B1 NO329351 B1 NO 329351B1

Authority

NO

Norway

Prior art keywords

chloro

hydrogen

methyl

benzimidazolyl

benzimidazolylamino

Prior art date

2002-06-04

Links

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• 239000003814 drug Substances 0.000 title claims abstract description 52
• 229940079593 drug Drugs 0.000 title claims abstract description 29
• 150000003577 thiophenes Chemical class 0.000 title abstract description 5
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 title description 20
• 229930192474 thiophene Natural products 0.000 title description 10
• 150000001875 compounds Chemical class 0.000 claims abstract description 104
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
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• 238000011321 prophylaxis Methods 0.000 claims abstract description 17
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• 230000003176 fibrotic effect Effects 0.000 claims abstract description 6
• 229910052739 hydrogen Inorganic materials 0.000 claims description 57
• 239000001257 hydrogen Substances 0.000 claims description 52
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
• 229910052731 fluorine Inorganic materials 0.000 claims description 25
• 239000000460 chlorine Substances 0.000 claims description 24
• 229910052801 chlorine Inorganic materials 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 22
• 229910052794 bromium Inorganic materials 0.000 claims description 20
• -1 compound compound Chemical class 0.000 claims description 19
• 238000004519 manufacturing process Methods 0.000 claims description 19
• 238000002360 preparation method Methods 0.000 claims description 15
• 210000000056 organ Anatomy 0.000 claims description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 11
• 229910052740 iodine Inorganic materials 0.000 claims description 11
• 208000020832 chronic kidney disease Diseases 0.000 claims description 10
• 150000002431 hydrogen Chemical class 0.000 claims description 10
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• 230000006378 damage Effects 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 201000001320 Atherosclerosis Diseases 0.000 claims description 8
• 230000010410 reperfusion Effects 0.000 claims description 8
• 208000028867 ischemia Diseases 0.000 claims description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 6
• 206010020772 Hypertension Diseases 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 239000011737 fluorine Substances 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 201000002859 sleep apnea Diseases 0.000 claims description 6
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 6
• 230000001684 chronic effect Effects 0.000 claims description 5
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• 208000035475 disorder Diseases 0.000 claims description 5
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• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
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• 201000011040 acute kidney failure Diseases 0.000 claims description 4
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
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• 238000003860 storage Methods 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
• 208000012998 acute renal failure Diseases 0.000 claims description 2
• 230000006793 arrhythmia Effects 0.000 claims description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
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• OUJWXEIDCSOWLT-UHFFFAOYSA-N n-(2-chloro-4-methylthiophen-3-yl)-n-methyl-1h-benzimidazol-2-amine Chemical compound N=1C2=CC=CC=C2NC=1N(C)C=1C(C)=CSC=1Cl OUJWXEIDCSOWLT-UHFFFAOYSA-N 0.000 claims description 2
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• 235000019439 ethyl acetate Nutrition 0.000 description 84
• 238000002844 melting Methods 0.000 description 74
• 230000008018 melting Effects 0.000 description 74
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• 229960000583 acetic acid Drugs 0.000 description 65
• 239000000243 solution Substances 0.000 description 57
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 56
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
• 239000012362 glacial acetic acid Substances 0.000 description 53
• 229910001868 water Inorganic materials 0.000 description 51
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• 238000000034 method Methods 0.000 description 47
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• 239000000203 mixture Substances 0.000 description 45
• 239000002904 solvent Substances 0.000 description 45
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 42
• 239000003112 inhibitor Substances 0.000 description 41
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
• 102100022897 Sodium/hydrogen exchanger 10 Human genes 0.000 description 36
• 239000007787 solid Substances 0.000 description 36
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
• 239000000741 silica gel Substances 0.000 description 33
• 229910002027 silica gel Inorganic materials 0.000 description 33
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
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• 238000004440 column chromatography Methods 0.000 description 17
• OQEAUWWCSIBKKC-UHFFFAOYSA-N 3-isothiocyanato-4-methylthiophene Chemical compound CC1=CSC=C1N=C=S OQEAUWWCSIBKKC-UHFFFAOYSA-N 0.000 description 16
• 235000011121 sodium hydroxide Nutrition 0.000 description 16
• 239000003480 eluent Substances 0.000 description 15
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• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
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• RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 3
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